tetano
Editor, Senior Moderator
Avian Pathol
. 2026 Jun 3:1-14.
doi: 10.1080/03079457.2026.2671739. Online ahead of print.
Comparative immunogenicity and cross-protection of wild-type and reverse genetics H5N8 (clade 2.3.4.4b) oil-adjuvanted vaccines against circulating H5N1 avian influenza viruses from clades 2.3.4.4b and 2.2.1.2
Ahmed Mohamed Abdelaal[SUP] 1 [/SUP], Sara H Mahmoud[SUP] 1 [/SUP], Mohamed Refaat Shehata[SUP] 2 [/SUP], Elsayed Tarek AbdElSalam[SUP] 3 [/SUP], Noura M Abo Shama[SUP] 1 [/SUP], Ahmed M Kandeil[SUP] 1 [/SUP], Mahmoud Shehata[SUP] 1 [/SUP], Mohamed A Ali[SUP] 1 [/SUP], Ahmed A Khalil[SUP] 4 [/SUP]
Affiliations
Highly pathogenic avian influenza (HPAI) H5N8 viruses of clade 2.3.4.4b continue to cause devastating outbreaks worldwide, necessitating effective vaccination strategies. The comparative efficacy of wild-type versus reverse genetics (RG)-based vaccine platforms against emerging H5Nx variants remains poorly characterized, particularly regarding cross-protective immunity mechanisms. We conducted a comprehensive comparative analysis of wild-type and RG-based H5N8 (clade 2.3.4.4b) oil-adjuvanted vaccines in specific-pathogen-free chickens (n = 150, power analysis based on detecting two-fold titre differences with 80% power, α = 0.05). Following single-dose vaccination, we assessed humoral and cellular immune responses, protection against homologous H5N8 (clade 2.3.4.4b), antigenically drifted and heterologous challenges [H5N1 clade 2.3.4.4b and H5N1 clade 2.2.1.2], and viral shedding dynamics using standardized assays. Both vaccines induced robust homologous antibody responses (HI titres: wild-type 7.2 ± 0.15 vs. RG 6.8 ± 0.13 log[SUB]2[/SUB], P < 0.05) by 28 days post-vaccination. Challenge studies revealed 100% protection against homologous H5N8 (clade 2.3.4.4b) for both vaccines, while wild-type vaccine demonstrated superior heterologous protection against H5N1 (clade 2.2.1.2): 60% vs. 40% (P = 0.04). Viral load quantification showed >3.0 log[SUB]10[/SUB] reduction in respiratory tissues, with strong correlation between HI titres and protection (r = 0.89, P < 0.001). Cellular immunity assessment revealed enhanced Th1-biased responses in wild-type vaccine recipients interferon-gamma/interleukin-4 (IFN-γ/IL-4 ratio: 1.61 vs. 1.49, P = 0.035), potentially explaining superior cross-protection. Wild-type H5N8 vaccines provided enhanced cross-protection compared to RG-based platforms while maintaining equivalent homologous efficacy. HI titres ≥4.5 log[SUB]2[/SUB] represent a critical threshold for protection, with optimal protection achieved at ≥6.0 log[SUB]2[/SUB]. These findings establish evidence-based correlates of protection and inform rational vaccine selection strategies for H5N8 control programs.
Keywords: Avian influenza; H5N8; Th1/Th2 balance; correlates of protection; cross-protection; reverse genetics; vaccine; viral shedding.
. 2026 Jun 3:1-14.
doi: 10.1080/03079457.2026.2671739. Online ahead of print.
Comparative immunogenicity and cross-protection of wild-type and reverse genetics H5N8 (clade 2.3.4.4b) oil-adjuvanted vaccines against circulating H5N1 avian influenza viruses from clades 2.3.4.4b and 2.2.1.2
Ahmed Mohamed Abdelaal[SUP] 1 [/SUP], Sara H Mahmoud[SUP] 1 [/SUP], Mohamed Refaat Shehata[SUP] 2 [/SUP], Elsayed Tarek AbdElSalam[SUP] 3 [/SUP], Noura M Abo Shama[SUP] 1 [/SUP], Ahmed M Kandeil[SUP] 1 [/SUP], Mahmoud Shehata[SUP] 1 [/SUP], Mohamed A Ali[SUP] 1 [/SUP], Ahmed A Khalil[SUP] 4 [/SUP]
Affiliations
- PMID: 42231810
- DOI: 10.1080/03079457.2026.2671739
Highly pathogenic avian influenza (HPAI) H5N8 viruses of clade 2.3.4.4b continue to cause devastating outbreaks worldwide, necessitating effective vaccination strategies. The comparative efficacy of wild-type versus reverse genetics (RG)-based vaccine platforms against emerging H5Nx variants remains poorly characterized, particularly regarding cross-protective immunity mechanisms. We conducted a comprehensive comparative analysis of wild-type and RG-based H5N8 (clade 2.3.4.4b) oil-adjuvanted vaccines in specific-pathogen-free chickens (n = 150, power analysis based on detecting two-fold titre differences with 80% power, α = 0.05). Following single-dose vaccination, we assessed humoral and cellular immune responses, protection against homologous H5N8 (clade 2.3.4.4b), antigenically drifted and heterologous challenges [H5N1 clade 2.3.4.4b and H5N1 clade 2.2.1.2], and viral shedding dynamics using standardized assays. Both vaccines induced robust homologous antibody responses (HI titres: wild-type 7.2 ± 0.15 vs. RG 6.8 ± 0.13 log[SUB]2[/SUB], P < 0.05) by 28 days post-vaccination. Challenge studies revealed 100% protection against homologous H5N8 (clade 2.3.4.4b) for both vaccines, while wild-type vaccine demonstrated superior heterologous protection against H5N1 (clade 2.2.1.2): 60% vs. 40% (P = 0.04). Viral load quantification showed >3.0 log[SUB]10[/SUB] reduction in respiratory tissues, with strong correlation between HI titres and protection (r = 0.89, P < 0.001). Cellular immunity assessment revealed enhanced Th1-biased responses in wild-type vaccine recipients interferon-gamma/interleukin-4 (IFN-γ/IL-4 ratio: 1.61 vs. 1.49, P = 0.035), potentially explaining superior cross-protection. Wild-type H5N8 vaccines provided enhanced cross-protection compared to RG-based platforms while maintaining equivalent homologous efficacy. HI titres ≥4.5 log[SUB]2[/SUB] represent a critical threshold for protection, with optimal protection achieved at ≥6.0 log[SUB]2[/SUB]. These findings establish evidence-based correlates of protection and inform rational vaccine selection strategies for H5N8 control programs.
Keywords: Avian influenza; H5N8; Th1/Th2 balance; correlates of protection; cross-protection; reverse genetics; vaccine; viral shedding.